The purpose of this project is to further study F-18 labeled biochemicals as probes for tumor detection using N-succinimidyl 4- [18P](fluoromethyl)benzoate as the labeling reagent. The advantage of using this radiolabeling agent is that agent can be made in one chemical step with a short synthesis time and high specific activity. After obtaining positive results using tumor mice for both biodistribution study and image study, further investigations were carried out using primates. Positron emission tomography imaging study with baboons using both fluorine-18 labeled transferrin and fluorine-18 labeled albumin showed that fluorine-18 labeled transferrin can be used to follow transferrin cellular internalization and efflux. In the future, this compound may be used to quantitate how efficiently transferrin- coupled compounds can be targeted to the liver. Studies of F-18 labeled dsFv were focused on how to decrease the kidney uptake. Two different approaches were used in the study, one by using amino acids to block the kidney uptake and the other by using a hydrolyzable linker to speed up the clearance of activity from kidney. Two new radiolabeling reagents were developed, one with proline as the linker and the other with lactic acid as the linker. Study showed that blocking is a more efficient way to reduce the kidney dose. Both native VIP and a VIP derivative were labeled using N-succinimidyl 4-[18F](fluoromethyl)-benzoate. Image studies using mice tumor model are under investigation. Two biotin derivatives were also labeled with N-succinimidyl 4-[18F](fluoromethyl)benzoate. Biodistribution study showed these two derivatives had similar blood clearance, but one derivative was more stable than the other. These labeled biotins will be used to target the tumor through a streptavidin-antibody conjugate system. A new F-18 labeled 5-HT1A ligand based on WAY-100635 has been developed. Synthesis of the derivatives is under way.